Thymidylate synthase messenger RNA (TYMS mRNA)

Thymidylate synthase messenger RNA (TYMS mRNA) is the transcript of the TYMS gene, which encodes the enzyme thymidylate synthase (EC 2.1.1.45). This enzyme catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), providing the sole de novo source of thymidylate required for DNA synthesis and repair (Source: UniProt P04818; NCBI Gene ID: 7298). A unique characteristic of TYMS mRNA is its involvement in a translational autoregulatory loop, where the thymidylate synthase protein binds to its own mRNA at the translational start site and within the protein-coding region to repress its own translation (Source: Chu et al., 1991, PNAS). In the presence of inhibitors like 5-fluorouracil (5-FU), the protein's binding affinity for the mRNA is reduced, leading to increased translation and elevated enzyme levels, which is a major mechanism of drug resistance (Source: Tai et al., 2004, Journal of Biological Chemistry). Consequently, TYMS mRNA is targeted by experimental antisense oligonucleotides and siRNA to deplete enzyme levels and bypass this feedback mechanism in various cancers, including colorectal, gastric, and breast cancer (Source: Lin et al., 2001, Molecular Cancer Therapeutics). High levels of TYMS mRNA expression are clinically recognized as a biomarker for poor prognosis and resistance to fluoropyrimidine-based therapies (Source: Popat et al., 2004, Journal of Clinical Oncology).

Other names

TS mRNAThymidylate synthetase mRNATYMS transcriptTYMS mRNA

Inhibition of translation through antisense binding or RNA interference, leading to mRNA degradation or physical blockage of the ribosome, thereby reducing the synthesis of the thymidylate synthase enzyme.